March 2014 Newsletter
March 2014 Newsletter - Spotlight on BRAF-Mutant Lung Cancers
Table of Contents
- President's Corner
- CEO Corner
- Upcoming Deadlines - IASLC Webinars & Events
- Special Features - Meet the Investigator * ELCC Notes
- News - EGFR Studies
- List of Events
Tony S.K. Mok, IASLC President
The Audi A3 Diesel and Volkswagen Golf Diesel are different cars. They look different, drive differently and are priced differently. However, the fact is that both cars use the exact same TDI (Turbocharged Direct Injection) engine. Should we consider them to be the same or different cars?
Melanoma and lung cancer are two different cancers. They look different, present differently and should be treated differently. But, for a specific type of lung cancer that share the same driver oncogene, namely BRAF V600E (even the name sounds like an engine), as melanoma. Should we consider them to be similar to BRAF V600E positive melanoma?
Melanoma driven by the BRAF V600E oncogene responds dramatically to BRAF tyrosine kinase inhibitors (TKI) including vemurafenib and dabrafenib, and median duration of response lasts more than 7 months. The pattern and duration of response is very similar to what we observe on the use of EGFR TKI in patients with EGFR mutation. BRAF inhibitor, such as dabrafenib, has been proven in randomized phase III studies to be safe and effective in BRAF V600E driven melanoma. The question is how we should investigate the role of dabrafenib in BRAF V600E driven lung cancer. The BRAF V600E mutation occurs in less than 2% of lung cancer and it will be exceedingly difficult and costly to conduct a randomized phase III study. Will a single-arm phase II study demonstrating high tumor response rate be sufficient? If so, where should we set the bar? This exercise will set an example of how we should investigate cross-cancer type driver oncogenes in future.
Two cars share one engine and two cancers share one driver oncogene. Are they similar or different? (Click here to read Tony Mok's President's Corner in simplified Chinese.)
Fred R. Hirsch, IASLC Chief Executive Officer
Education is an IASLC core activity, and we are continuously expanding our educational programs. Our monthly webinar series has experienced great success, and many new topics are planned for 2014. We are also expanding webinars in Asia, including the upcoming webinar on “Personalized Medicine for NSCLC” led by Dr. Mok.
The development of educational programs for community practices, particularly in the US, has been a priority for 2014. Together with the Educational Committee, we are currently developing multidisciplinary educational programs for smaller audiences including expert faculties representing different specialties with focus on lung cancer. We also hope to expand such a program also to other parts of the world.
The IASLC Fellowship Committee has recently finished the evaluation of the many applicants for the 2014-2015 Fellowship Awards and the Board of Directors has made the final approval. The Award winners will be notified within the next weeks.
Our Publication Program is moving forward. The IASLC Multidisciplinary Textbook with Chief Editor Harvey Pass and Co-Editors Giorgio Scagliotti and David Ball will be ready for launch at ASCO 2014.
The IASLC ALK-Atlas has received requests beyond expectations and is currently being translated to Chinese and Japanese, and a Spanish edition is planned. Our Pathology Committee is diligently working on a new edition of the WHO/IASLC classification of malignant lung tumors, and the book is planned to be finished by beginning of 2015. Likewise, our Staging Committee is also currently working on an update of the international staging classification, which currently is planned to be completed in 2015-2016.
Our meeting activities are moving successfully forward. After a very successful meeting focusing on lung cancer biology joined with AACR, we just completed the European Lung Cancer Conference (ELCC) together with ESMO. Nearly 1500 participants joined this meeting in Geneva, Switzerland. The programs for our other regional meetings are also moving forward; Latin American lung Cancer Meeting in Peru in August and Asian Pacific Lung Cancer Meeting in Kuala Lumpur, Malaysia in November and Chicago Meeting for North America in the end of October-beginning of November. We hope as many as possible of our members will join these regional meetings.
The final part of our “Best of WCLC” series is underway. Once completed, 18 sites in the US, Latin America, Europe and Asia will have successfully distributed the scientific achievements presented in Sydney through the Best of WCLC Program. Preparations are currently ongoing for the next World Conference on Lung Cancer in Denver 2015 and several new educational tracks will be introduced at that meeting, such as tracks for community doctors and allied health care personnel, as well as special tracks for nurses and advocates.
Finally, but not least, the IASLC Headquarters have put much effort into improvement of our web site and portals these days. While our IT effort is a continuous effort, we hope that our web site is serving our members and non-members well in education and updates on lung cancer and the IASLC activities.
WEBINAR: Special Asia Webinar - A Molecular Era in Lung Cancer: 2014 - April 17, 2014
Join Dr. Tony Mok and an internationally-renowned faculty as they provide a concise and relevant view of the state-of-the-art of targeted, molecular -based therapy of lung cancer. View Details
WEBINAR: Chemotherapy for Advanced NSCLC: State-of-the-Art in 2014 - April 22, 2014
IASLC Grand Rounds (CME): A Monthly Series of Live Webinars. 4th Webinar: Chemotherapy for Advanced NSCLC: State-of-the-Art in 2014 (Georgio Scagliotti, MD) April 22, 2014 at 8:00 PM EDT. View Details
Abstract Submission Open for Chicago Multidisciplinary Symposium in Thoracic Oncology - Due May 7, 2014
The abstract submission site is now open for the Chicago Multidisciplinary Symposium in Thoracic Oncology, taking place October 30-November 1, 2014, at the Chicago Marriott Downtown Magnificent Mile. This biennial, two-and-a-half day symposium is designed to provide a clinically relevant multidisciplinary update on the scientific progress in treating thoracic malignancies. The meeting is co-sponsored by ASTRO, ASCO, IASLC and the University of Chicago. Abstracts will be accepted through May 7, 2014, at 11:59 p.m. Eastern time. Visit the abstract site for submission categories and guidelines and to submit an abstract.
Registration Now Open for Asia-Pacific Lung Cancer Conference
We are delighted to announce that registration is now open for the 2014 IASLC Asia Pacific Lung Cancer Conference (APLCC 2014) which will be held in Kuala Lumpur, Malaysia from 6 to 8 November 2014. Register Online Now
All IASLC Meeting Information
To see the full schedule of IASLC Meetings, visit our event page.
Meet the Investigator - Spotlight on BRAF - David Planchard, MD, PhD
Insitut Gustave Roussy, Department of Medical Oncology, France
Primary Specialty: Pulmonary Oncology
Q1. Please tell our members what clinical trials are currently accruing patients with BRAF-mutant lung cancers.
Currently only one study focused on BRAF mutated NSCLC (stage IV) patients is recruiting. This study is testing dabrafenib as a single agent versus in combination with trametinib. Patients in the single agent can cross-over to the combination treatment upon radiologic disease progression. Other studies are forthcoming, e.g. LGX818 inhibitor.
Q2. Please commend on the breakthrough status for dabrafenib.
While frequent in malignant melanoma (>50%), activating BRAFV600E-mutations in NSCLC are rare (2%), and primarily in adenocarcinoma. The potent and selective BRAF-small molecule inhibitor dabrafenib has demonstrated clinical activity in BRAFV600-mutation positive melanoma. We reported at ASCO 2013 (D.Planchard et al, abstract N° 8009) the preliminary results of a single-arm phase II study in Stage IV BRAFV600E mutation-positive NSCLC pts who failed at least one line of conventional chemotherapy. Dabrafenib shows early clinical activity in BRAF V600E mutation positive NSCLC pts with an overall response rate of 54% and duration of response of up to 49 weeks. With an overall disease control rate of 60%, partial response was seen in 40% of patients and stable disease was seen in 20% of patients. Disease progression was reported for 30% of patients. At the time of data cut for this analysis, 12 (48%) patients remain on therapy, and 13 (52%) had stopped therapy. Safety of dabrafenib in NSCLC pts appears to be consistent with what has been previously observed. Although BRAF V600E is an actionable target in NSCLC, it is not known how long the efficacy of dabrafenib will last. U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for Tafinlar® (dabrafenib) for treatment of patients with metastatic BRAF V600E mutation-positive NSCLC who have received at least one prior line of platinum-containing chemotherapy.
Q3. Please comment on any differences in activity of BRAF inhibitors in melanoma, NSCLC, CRC.
BRAF inhibitors like vemurafenib or dabrafenib appear to be highly efficacious in melanoma patients with BRAF V600E mutations, with response rates of approximately 50% and progression-free survival of 6 months. There is data to suggest that dabrafenib not only shows activity in V600E-mutated melanoma, but also in non-V600E BRAF-mutated disease such as V600K. Similar results have been observed in BRAF-mutated NSCLC treated with dabrafenib. The U.S. Food and Drug Administration and European Medicines Agency have approved dabrafenib as a single agent for the treatment of unresectable or metastatic melanoma in adult patients with BRAF V600E mutation. More recently results from an open-label phase I/II trial showed that trametinib combined with dabrafenib nearly doubled the duration of response and significantly improved overall response rates when compared with dabrafenib alone (Flaherty KT, et al. N Engl J Med. 2012). Trametinib has been approved for use in combination with dabrafenib for unresectable or metastatic melanoma with BRAF V600E or V600K mutations. Although BRAF V600E is an actionable target in NSCLC, it is not known how long the efficacy of dabrafenib will last. Also, the association of dabrafenib and trametinib is being tested in NSCLC and the best therapy may be a combination of BRAF and MEK inhibitors in BRAF-mutated NSLC patients. Clinical activity of trametinib and dabrafenib is currently being tested in combination with an anti-EGFR antibody in subjects with BRAF-mutated (V600E or V600K) colorectal cancer. The BRAF V600 mutation occurs in 5-10% of metastatic CRC. (Click here to read in simplified Chinese.)
IASLC/ESMO 4th European Lung Cancer Conference (March 26-29) - Update from Enriqueta Felip and Rafal Dziaziuszko, Conference Co-Chairs
It is a great honour for us to have the opportunity to collaborate in organizing this 4th European Lung Cancer Conference. During this meeting top academic experts in thoracic malignancies from different disciplines discussed the latest developments in this field, in clinical, translational and basic research. The ELCC conference provided a significant amount of data on immunomodulation, a promising new approach in lung cancer, and the integration of molecular testing in our clinical practice.
At the ELCC 2014 new data from outstanding relevant studies was presented in the proffered paper sessions. The main themes discussed in the educational sessions during the Conference were:
- Molecular testing in advanced NSCLC: clinical practice, clinical trials, emerging biomarkers
- Immunotherapy in NSCLC: new findings and how to select patients for this approach
- Oncogenic-driven diseases: potential role of local therapies, strategies for overcoming resistance
- Targeted therapies: new developments
- Advanced NSCLC in the absence of driver mutations: treatment approaches
- Oligometastatic NSCLC: definition, biology, changing the role of local treatments
- Mesothelioma: standards and controversies
The ELCC 2014 meeting provided an opportunity to meet top multidisciplinary experts in the thoracic malignancy field and to network with all those interested in how to translate new discoveries into better diagnosis, staging and treatment of thoracic malignancies. The meeting has been an excellent place to create new contacts, to share new ideas for projects and to promote collaboration in thoracic malignancy research. (Click here to read the ELCC Preview in Chinese.)
**CORRECTION To February Newsletter: The original statement was written as follows: "On the last day [of the IASLC 14th Annual Targeted Therapies of the Treatment of Lung Cancer meeting] it was announced that the VEGFR2 human antibody ramucirumab was associated with prolonged survival in the pivotal trial comparing second line chemotherapy alone to second line therapy with ramucirumab in non-squamous cell lung cancer. Many new antibody therapies and novel drug conjugates were also discussed. One of the highlights was the presentations of novel data by fellows and young investigators….” In fact, the statement should have read: The above mentioned study evaluated the effect of combination therapy with ramucirumab and docetaxel on the survival of patients with non-squamous and squamous lung cancer. IASLC apologizes for the omission.
Characteristics of Lung Cancers arising in Germline EGFR T790M Mutation Carriers and Relationship to Smoking Status
In April Journal of Thoracic Oncology, two studies are providing new insight into germline epidermal growth factor receptor (EGFR) T790M mutation in familial non-small cell lung cancer (NSCLC). The findings suggest the need for tailored approaches for early detection and treatment, as well as for genetic testing to identify carriers. Read More
To read an interview with Adi Gazdar, MD, PhD about his study and it's implications for clinicians and patients, visit MedicalResearch.com.
Erlotinib and Gefitinib Offer Similar Benefit in NSCLC with EGFR Mutation - First Direct Comparison of Drugs in this Population
Also in April JTO, a retrospective study has shown that two targeted therapy drugs achieved similar outcomes among people with metastatic or recurrent non-small cell lung cancer (NSCLC) harboring an EGFR mutation. Read More
IASLC Develops Education Curricula
The IASLC Education Committee is developing CME Curriculum for Medical Oncology and for Surgical or Thoracic Oncology. Details on the CME Curricula will be released once available.
IASLC ALK Atlas now Available for Apple and Android
The new IASLC Atlas of ALK Testing in Lung Cancer is designed to help pathologists, laboratory scientists, and practicing physicians better understand the background, protocol, and the interpretation of results of ALK testing in patients. The Atlas is now available for downloading to iPhones, iPads and Android devices. Just like the book, the app addresses methods of testing and interpretation. With the added capability of search and extensive links the app engages the reader in the latest science. The app is available to download from the Apple iTunes App Store or the Android Google Play Store for U.S. $4.99. Published in conjunction with Editorial Rx Press and with the support of Pfizer, Inc., the IASLC Atlas of ALK Testing in Lung Cancer was first distributed to attendees at the recent IASLC World Conference on Lung Cancer in Sydney, Australia. A view only version is available here. Additional distribution channels are expected to be announced in the coming weeks.
The IASLC Multidisciplinary Approach to Thoracic Oncology, scheduled for publication in June 2014, is designed to be the authoritative educational resource in the complex field of thoracic oncology. Led by Executive Editor Harvey I. Pass, MD, and Editors David Ball, MD, FRANZCR and Giorgio V. Scagliotti, MD, this textbook is written for thoracic cancer specialists and IASLC members worldwide who are dedicated to enhancing their knowledge in an ever-changing oncology subspecialty. The IASLC Multidisciplinary Approach to Thoracic Oncology will expand on the basics of thoracic oncology as well as be a primer on new concepts in the field. The book will be available both in print and electronically. Electronic updates will be available digitally to provide the latest scientific information and keep readers informed and current.
IASLC 2014 Renew Now to Avoid JTO Service Interruption - 3-year Membership Now Available
All Members will begin receiving their member renewal notices via email. Please note that IASLC dues for Regular Members from developed countries have increased to $250.00, while dues for Developing Country and Allied Health Professional Members remain $50.00.
There are new options for each member category and Regular Members from developed countries may "lock-in" the previous member rates, and save $150.00 over three years by selecting the 3-year Membership option ($600.00).
We encourage all members to renew early so we can ensure you have no interruption of benefits or JTO delivery and online access. Please review the single-year and multi-year options available to you!
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Journal of Thoracic Oncology
The IASLC’s premier journal, emphasizing a multidisciplinary approach including original research (clinical trials and translational or basic research), reviews and opinion pieces. Visit JTO